BACKGROUND: The treatment of melanoma in situ (MIS), particularly the lentigo maligna (LM) subtype, has been a controversial subject in the literature for over a decade. Surgical excision with 5 mm margins is the standard of care in the USA, while several variations of Mohs surgery are frequently used to treat clinically ill-defined lesions. Radiation is much less frequently used. Topical imiquimod has also been more recently proposed, in small case reports in the literature, as a therapy for MIS. However, controversies exist with all approaches. OBJECTIVE: To review the current literature regarding topical imiquimod, radiation therapy, surgical excision, and the various forms of Mohs surgery for MIS, focusing on the LM subtype. METHODS: A literature search was performed in the PubMed database using the following terms: "melanoma in situ,""lentigo maligna,""excisional surgery,""Mohs micrographic surgery,""radiation therapy," and "imiquimod." Articles relevant to the treatment of MIS were reviewed and reported herein. RESULTS: Studies of imiquimod therapy for MIS are hampered by small study numbers and short follow-up periods. The few, better-designed studies reveal relatively low cure rates. In addition, literature review reveals that a significant percentage of cases of MIS that are initially diagnosed as in situ disease by biopsy subsequently prove to have an invasive component upon complete excision. This finding suggests that topical therapy of any kind may be problematic. Studies of radiation therapy for MIS have relatively small numbers of patients and short follow-up. Multiple studies of excisional surgery have shown that 5 mm margins are often insufficient to clear the LM subtype of MIS due to unseen subclinical extension, accounting for this treatment's reported 8-20% recurrence rate. Finally, a number of variants of traditional frozen section Mohs surgery have been utilized to try and achieve complete peripheral margin assessment of clinically ill-defined LM lesions. All studies are retrospective, and most are single-institution and frequently single-operator, limiting the meaningfulness of their results. Nevertheless, they involve moderate numbers of patients, and many have at least a five year follow-up. Collectively, they suggest recurrence rates in the range of 0.5-3.0%. CONCLUSION: Topical imiquimod therapy appears to provide relatively low cure rates for MIS, and because some of these lesions contain an unrecognized invasive component, should be used with extreme caution to treat this disease. Radiation therapy may be a useful second-line therapy if surgery is contraindicated. Excisional surgery is an appropriate therapy for clinically well-defined MIS; however, margins larger than 5 mm may be required when treating larger or indistinct lesions. Finally, for clinically ill-defined LM arising on sun-damaged skin, especially in regions of aesthetic concern, some form of complete peripheral margin assessment - one of the various forms of Mohs surgery - may provide the highest cure rate and create the smallest surgical defect.
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